Tumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC

// Teng-Fei Fan 1, * , Lin-Lin Bu 1, * , Wei-Ming Wang 1 , Si-Rui Ma 1 , Jian-Feng Liu 1 , Wei-Wei Deng 1 , Liang Mao 1 , Guang-Tao Yu 1 , Cong-Fa Huang 1 , Bing Liu 2 , Wen-Feng Zhang 1, 2 , Zhi-Jun Sun 1, 2 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China 2 Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China * These authors have contributed equally to this work Correspondence to: Zhi-Jun Sun, e-mail: zhijundejia@163.com Wen-Feng Zhang, e-mail: zhangwf59@whu.edu.cn Keywords: autophagy, STAT3, head and neck cancer, apoptosis Received: July 06, 2015      Accepted: October 20, 2015      Published: October 30, 2015 ABSTRACT Autophagy is considered as a double-edged sword. It can prolong the survival of cancer cells and enhance its resistance to apoptosis, and paradoxically, defective autophagy has been linked to increased tumorigenesis, but the mechanism behind this phenomenon is unclear. In this study, we demonstrated that decreased phosphorylation of signal transducer and activator of transcription 3 ( p -STAT3) was correlated with increased autophagy through the Akt/mTOR and Erk signaling pathways in human head and neck squamous cell carcinoma (HNSCC). We also showed that blockage of STAT3 by NSC74859 could markedly induce apoptotic cell death and autophagy. Meanwhile, increased autophagy inhibited apoptosis. The pharmacological or genetic inhibition of autophagy and STAT3 further sensitized HNSCC cells to apoptosis. Furthermore, evidence from xenograft model proved that suppressed STAT3 activity combined with inhibition of autophagy promoted tumor regression better than either treatment alone. Taken together, this present study demonstrated that autophagy alleviates apoptotic cell death in HNSCC, and combination of inhibition of STAT3 by NSC74859 and autophagy might be a promising new therapeutic strategy for HNSCC.